Catalytic Synthesis and Characterization of Biodegradable ...

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Polymerization and Applications of Biodegradable Polyesters
paramagnetic nitroxyl radical may be reduced to diamagnetic hydroxylamine with the loss of
T1 MR relaxation in the internal reduction environment.
Figure 1.6.7 illustration of HPS-TEMPO.
To address the abovementioned issues, several strategies have been reported, including
conjugation of nitroxyl radical compounds with dendritic/hyperbranched polymers or
copolymerization with hydrophilic monomers. As an example, Winalski et al. 197 reported to
find that the fourth-generation polypropylenimide-(DAB) and third-generation
polyamidoamide-(PAMAM) dendrimer-linked nitroxides had greater relaxivity than
Gd-DTPA and the selective enhance contrast were observed in healthy articular cartilage. The
relaxivities of the compounds were found to increase as the increase of nitroxides that
incorporated in the dendrimers. This result was also observed by Ghandehari et al. and Koga
et al.. Koga and co-workers have synthesized a series of high water-soluble hyperbranched
poly(styrene) (HPS) carrying stable TEMPO radicals (Figure 1.6.7). 198 The relaxivity 14
mM -1 s -1 , which is comparable with commercial Gd-DTPA agent, could be obtained when
high density of TEMPO radicals has been conjugated with the polymers. Studies by
Ghandehari et al. 199 have been reported that N-(2-hydroxylpropyl)methacryamide (HPMA)
copolymer-linked nitroxides were synthesized for potential MRI application. The HPMA
monomer was firstly copolymerized with reactive MAGGONp monomer and then chemical
link with the nitroxides was performed via reactive MAGGONp residues. The relaxicities of
the copolymers bearing nitroxides were found to be linear dependent on the nitroxides
content in the copolymers which is consistent with the previous report by Winalski et al..
Another strategy has also proposed by Gussoni and co-workers. 200 They have synthesized
pH-sensitive poly(amidoamine)s containing TEMPO radicals in the backbone. Though the
relaxicity was measured to be not too high, the polymers were found to be tendency to
accumulate in the tumor for a sufficient time.